Project Summary: The objective of this application is for Wayne State University (WSU) to continue as a Maternal-Fetal Medicine Unit (MFMU) Network site. We are committed to cooperative research and offer a large patient base (9,800 deliveries/year), including a high percentage of minorities, from which to enroll into network protocols. We propose to achieve this objective with WSU MFMU highly qualified research team, which has strong leadership, with knowledge and experience in research design and collaboration in multicenter randomized clinical trials, as well as adequate time commitment and resources for performance of Network studies. Our capability and intent of recruitment, rigorous patient evaluations and treatment of subjects using common protocols are documented by both current status and past performance. WSU is tied for 4th in ranking for enrollment during the current cycle. WSU contributed 23.8% of pregnant women of African American descent into MFMU studies. It is our expectation that we will continue to be an integral and contributing member of the MFMU in research, identified by other members as innovators of new projects. Sixteen subspecialists in maternal-fetal medicine (three also subspecialized in clinical genetics), and two neonatologists will collaborate in the MFMU Network Center. Our computerized perinatal database now contains over 145,736 deliveries. Our long-range research goal is to develop strategies for the prevention of preterm birth. The central hypothesis of the concept proposal is that treatment with 17 Hydroxyprogesterone Caproate (17-OHP) reduces the risk of preterm birth in women who have previously experienced a midtrimester spontaneous pregnancy loss, or experience mid-trimester vaginal bleeding in the current pregnancy. The specific aims are to identify women with a spontaneous pregnancy loss at 13-20 weeks in prior pregnancy or with presence of vaginal bleeding at 13-20 weeks in the current pregnancy, and to test the effectiveness of treatment with 17-OHP to reduce the rate of PTB. The concept proposal is a randomized, double-blind, placebo controlled, multicenter trial. The proposed research is innovative for its study design, patient selection, and utility of survival analysis. The outcomes will be significant because the will provide stronger foundation for treatment with 17-OHP. Our application and research proposal will reduce preterm delivery, and improve the health of pregnant women, their fetuses, and neonates.